Comparative analysis of interleukin 15 and interleukin 2 for induction of killer activity and of type 2 cytokine production by mononuclear cells from lung cancer patients

Abstract

Summary Interleukin (IL) 15 is a novel cytokine with IL-2-like activity. In this study, we examined the effect of IL-15 on induction of non major histocompatability complex (MHC)-restricted killer activity and of type 2 cytokine production by peripheral blood and pleural mononuclear cells (MNCs), from 34 lung cancer patients and 20 control subjects. Interleukin 15 (IL-15) is a novel M 15 000 cmtokine and has similar biological activities to those of IL-2: it induces T-cell proliferation. enhances natural killer (NK) cell cytotoxicity and up-regulates production of NK cell-derived cytokines (Carson et al. 1994). Recently. attention has been focused on the clinical application of IL-15 for cancer immunotherapy (Gamero et al. 1995) and. for effective clinical application of IL-15. at least two problems must be solved. We have already demonstrated that the presence of a malignant neoplasm affects various host functions (Sone et al. 1990: Nabioullin et al. 1995. Therefore. the first problem is whether the presence of lung cancer affects the induction of non-major histocompatibility complex (MHC)-restricted killer activity by 1L-15.The second problem is to evaluate type 2 cytokine production by IL-15-activated mononuclear cells (MNCs). because the growth of cancer cells is regulated by the cytokine network. via autocrine and paracrine pathways. in situ. In the analysis of the cytokine network. two distinct cytokine patterns generated by T lymphocytes can be considered (Mosmann et al. 1986 (Yamamura et al. 1993: Kharkvitch et al. 1994). Production of type 2 cytokines by lung cancer has been reported (Hung et al. 1995). and immunotherapy with cytokines may alter this type 2 predominant pattern of the type 1/type 2 axis.In this work. we studied the effect of L-15 alone or in combination with L-12 on the immune function of MNCs from lung cancer patients. in terms of expression of non-MHC-restricted killer activity and type 2 cytokine production. MATERIALS AND METHODSPatients with lung cancer and control patients Thirty-four patients with primary lung cancer were studied after obtaining informed consent. Of these. 24 were men and ten were women aged 36-83 years (median age 67 years). Histological examinations revealed that 17 patients had adenocarcinoma. nine had squamous cell carcinoma. five had small-cell carcinoma and three had large-cell carcinoma. Staging examination revealed that 17 patients were stage IV. ten were stage IIIB. four were stage I11A. two were stage H and one was stage I. Nine patients had malignant pleural effusion. They had received no anti-cancer therapy before this study. Twenty subjects were studied as controls. Of these. nine subjects were control patients (three males and six females) aged 22-82 years (median age 42 years). Examinations revealed no malignant lesions or autoimmune diseases in these nine patients. The other 11 control subjects (nine men and two women) were healthy volunteers who had no signs of infection. were not taking medication and were aged 22-48 years (median age 28 ye...

Suppression of IL-2-Induced T Cell Proliferation and Phosphorylation of STAT3 and STAT5 by Tumor-Derived TGFβ Is Reversed by IL-15

“…In the setting of tumor and HIV immunotherapy, IL-15 provides hope that where T cell responses to IL-2 are inefficient or defective they can be reactivated (29,30). However, administration of IL-15 to patients is potentially risky, as IL-15 is implicated in the pathogenesis of autoimmune diseases such as rheumatoid arthritis (31), and in the case of MM, potentially could act as a tumor cell survival factor (32,33).…”

Synthesis and Secretion of Interleukin-15 by Freshly Isolated Human Bronchial Epithelial Cells

“…IL-15, a novel cytokine initially identified in culture supernatants of the kidney epithelial cell line CV-I/EBNA, stimulates proliferation, activation and recruitment of T and B cells, natural killer (NK) cells and lymphokine-activated killer cells through interaction with components of the IL-2Rβ and γ chains in addition to its unique binding protein (IL-15Rα) [10, 11, 12, 13, 14, 15, 16]. Unlike IL-2, IL-15 gene expression has been reported in various tissues and cells including lung adenocarcinoma cell line [17].…”

Modulation of Interleukin-15-Induced Human Neutrophil Responses by the Plant Lectin Viscum album Agglutinin-I

“…In addition, tumor cells engineered to secrete IL-15 were found to increase anti-tumor immune responses in vivo (36). Takeuchi and colleagues have studied IL-15-induced human killer cell activity against lung cancer cell lines and concluded that this cytokine has the potential for lung cancer immunotherapy (37). One study has compared the toxicity and anti-tumor efficacy of IL-15 with IL-2 in the context of syngeneic bone marrow transplantation.…”

“…This attests to the complexity of the biological activity of IL-15. On one hand, this cytokine may possess some anti-tumor properties (11,12), whereas, on the one other hand, it may also possess proinflammatory properties (14,15).…”

“…IL-15 is a proinflammatory cytokine that possesses some anti-tumor activities (11,12). This cytokine is known to mediate its biological activity by binding to a specific cell surface receptor, the IL-15R.…”